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Author Notes:

Corresponding author: Jennifer Gladys Mulle, Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, P: (404) 727-3042, F: (404-727-3949), jmulle@emory.edu

GJB, TC, JGM, STW and DW designed the research.

TR, RP and RP performed research with help from GG, SG, UK, RP, TM and JPS. ME, TR and RP analyzed data.

TC, JGM, TR and DW wrote the manuscript.

All authors provided edits and approved final manuscript.

We are grateful to Dr. Jeffrey Miner, Washington University in St Louis, for providing Dlg1 mutant mice.

The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.

The authors have nothing to disclose.


Research Funding:

The work was supported by R01GM097331 (TC, DW, STW), R56MH116994 (TC, JM, DW, STW) and R01MH110701 along with funds from the Department of Human Genetics at Emory.

This study was supported in part by the Mouse Transgenic and Gene Targeting Core (TMF) and the Rodent Behavioral Core, which are subsidized by the Emory University School of Medicine and are part of the Emory Integrated Core Facilities.

Additional support was provided by the Georgia Clinical & Translational Science Alliance of the National Institutes of Health under Award NumberUL1TR002378

This study was also supported by the Emory Winship Research Pathology Core Lab

Behavioral changes and growth deficits in a CRISPR engineered mouse model of the schizophrenia-associated 3q29 deletion

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Journal Title:

Molecular Psychiatry


Type of Work:

Article | Post-print: After Peer Review


The 3q29 deletion confers increased risk for neuropsychiatric phenotypes including intellectual disability, autism spectrum disorder, generalized anxiety disorder, and a >40-fold increased risk for schizophrenia. To investigate consequences of the 3q29 deletion in an experimental system, we used CRISPR/Cas9 technology to introduce a heterozygous deletion into the syntenic interval on C57BL/6 mouse chromosome 16. mRNA abundance for 20 of the 21 genes in the interval was reduced by ~50%, while protein levels were reduced for only a subset of these, suggesting a compensatory mechanism. Mice harboring the deletion manifested behavioral impairments in multiple domains including social interaction, cognitive function, acoustic startle, and amphetamine sensitivity, with some sex-dependent manifestations. In addition, 3q29 deletion mice showed reduced body weight throughout development consistent with the phenotype of 3q29 deletion syndrome patients. Of the genes within the interval, DLG1 has been hypothesized as a contributor to the neuropsychiatric phenotypes. However, we show that Dlg1 +/- mice did not exhibit the behavioral deficits seen in mice harboring the full 3q29 deletion. These data demonstrate the following: the 3q29 deletion mice are a valuable experimental system that can be used to interrogate the biology of 3q29 deletion syndrome; behavioral manifestations of the 3q29 deletion may have sex-dependent effects; and mouse-specific behavior phenotypes associated with the 3q29 deletion are not solely due to haploinsufficiency of Dlg1.

Copyright information:

© 2019, Springer Nature Limited.

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